Mdt1 facilitates efficient repair of blocked DNA double-strand breaks and recombinational maintenance of telomeres.
DNA recombination plays critical roles in DNA repair and alternative telomere maintenance. Here we show that absence of the SQ/TQ cluster domain-containing protein Mdt1 (Ybl051c) renders Saccharomyces cerevisiae particularly hypersensitive to bleomycin, a drug that causes 3'-phospho-glycolate-blocked DNA double-strand breaks (DSBs). mdt1Delta also hypersensitizes partially recombination-defective cells to camptothecin-induced 3'-phospho-tyrosyl ... protein-blocked DSBs. Remarkably, whereas mdt1Delta cells are unable to restore broken chromosomes after bleomycin treatment, they efficiently repair "clean" endonuclease-generated DSBs. Epistasis analyses indicate that MDT1 acts in the repair of bleomycin-induced DSBs by regulating the efficiency of the homologous recombination pathway as well as telomere-related functions of the KU complex. Moreover, mdt1Delta leads to severe synthetic growth defects with a deletion of the recombination facilitator and telomere-positioning factor gene CTF18 already in the absence of exogenous DNA damage. Importantly, mdt1Delta causes a dramatic shift from the usually prevalent type II to the less-efficient type I pathway of recombinational telomere maintenance in the absence of telomerase in liquid senescence assays. As telomeres resemble protein-blocked DSBs, the results indicate that Mdt1 acts in a novel blocked-end-specific recombination pathway that is required for the efficiency of both drug-induced DSB repair and telomerase-independent telomere maintenance.
Mesh Terms:
Antibiotics, Antineoplastic, Antigens, Nuclear, Antineoplastic Agents, Phytogenic, Bleomycin, Camptothecin, DNA Damage, DNA Repair, DNA, Fungal, DNA-Binding Proteins, Epistasis, Genetic, Rad52 DNA Repair and Recombination Protein, Recombination, Genetic, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Telomere
Antibiotics, Antineoplastic, Antigens, Nuclear, Antineoplastic Agents, Phytogenic, Bleomycin, Camptothecin, DNA Damage, DNA Repair, DNA, Fungal, DNA-Binding Proteins, Epistasis, Genetic, Rad52 DNA Repair and Recombination Protein, Recombination, Genetic, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Telomere
Mol. Cell. Biol.
Date: Sep. 01, 2007
PubMed ID: 17636027
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